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Scientists discovered years ago that newborn infants depend upon immune components transferred from their mothers to survive the onslaught of pathogens that begin invading their bodies as soon as they are born. Eventually, children develop their own immune systems, built through surviving natural exposures to viruses and bacteria, and augmented by a phalanx of well-established childhood vaccines. But in the meantime, it's one of a mother's most important gifts that keeps their babies safe: antibodies. Now, a far-reaching study published June 8, 2022, in Nature, provides a surprising explanation of how those early days of mother-provided immunity actually work-and what that information could mean for preventing death and disability from a wide range of infectious diseases. The findings suggest that researchers may be able to mimic the amped-up antibodies that expecting mothers produce to create new drugs to treat diseases as well as improved vaccines to prevent them. “For many years, scientists believed that antibodies cannot get inside cells. They don't have the necessary machinery. And so, infections caused by pathogens that live exclusively inside cells were thought to be invisible to antibody-based therapies,” says Sing Sing Way, MD, PhD, Division of Infectious Diseases at Cincinnati Children's. “Our findings show that pregnancy changes the structure of certain sugars attached to the antibodies, which allows them to protect babies from infection by a much wider range of pathogens.” “The maternal-infant dyad is so special. It's the intimate connection between a mother and her baby,” says John Erickson, MD, PhD, Division of Neonatology, and first-author of the study. Both Way and Erickson are part of Cincinnati Children's Center for Inflammation and Tolerance and the Perinatal Institute, which strives to improve outcomes for all pregnant women and their newborns. Erickson continues, “This special connection starts when babies are in the womb and continues after birth. I love seeing the closeness between mothers and their babies in our newborn care units. This discovery paves the way for pioneering new therapies that can specifically target infections in pregnant mothers and newborns babies. I believe these findings also will have far-reaching implications for antibody-based therapies in other fields.” STUDY ADDRESSES A ‘SILENT EPIDEMIC' While COVID-19 has reminded the world of the scale of a pandemic, infections from various pathogens combine to kill 2 to 3 million infants and mothers a year worldwide, Way says. This study explored, in mice, the interactions between antibodies and Listeria monocytogenes, a common bacteria that replicates primarily within cells. Pregnant women are 10 times more likely than women in general to become infected by Listeria. Severe infections can lead to miscarriages, stillbirths, preterm labor, and serious illness or death in newborns. For years, scientists believed the bacteria was unreachable by antibodies. But the Cincinnati Children's team showed that during pregnancy, Listeria can be targeted by antibodies. Way says the scientific world tends to focus on non-pregnant states during pre-clinical studies, and generally avoids conducting clinical drug research involving pregnant women. This can mean that biological changes that affect the immune system during pregnancy also can be overlooked. “If we had not approached this with the goal of understanding the maternal-fetal dyad, we would not have found this unique naturally-occurring shift in antibody structure,” Way says. How mothers make super antibodies The new study identifies which specific sugar is changed during pregnancy, as well as how and when the change occurs. During pregnancy, the "acetylated" form of sialic acid (one of the sugars attached to antibodies) shifts to the "deacetylated" form. This very subtle molecular change allows immunoglobulin G (IgG) -- the body's most common type of antibody -- to take on an expanded protective role by stimulating immunity through receptors that respond specifically to deacetylated sugars. "This change is the light switch that allows maternal antibodies to protect babies against infection inside cells," Way says. "Mothers always seem to know best," Erickson adds.